Apparatus for separation of blood components

ABSTRACT

An apparatus for the separation of blood components, specifically for the removal of white blood cells and blood platelets from blood comprises a tubular housing providing at one end thereof with a blood inlet and at the other end thereof with a blood outlet and an aggregate layer of fibers capable of sequestering white blood cells and blood platelets packed in the housing. The aggregate layer of fibers comprises a blood inlet side layer of a bulk density of not less than 0.16 g/cm 3  and less than 0.21 g/cm 3  and a blood outlet side layer of a bulk density of not less than 0.21 g/cm 3  and not more than 0.23 g/cm 3  and is packed in a ratio in the range of 0.04 to 0.09 g per ml of the flow volume of blood under treatment.

TECHNICAL FIELD

This invention relates to an apparatus for the separation of bloodcomponents. More particularly, it relates to an apparatus for theseparation of blood components, specifically for the removal of whiteblood cells and blood platelets from blood.

BACKGROUND ART

Heretofore in the therapy by blood transfusion, more often than notwhole-blood preparations of red blood cell preparations have been used.These preparations, however, inevitably contain the white blood cellantibody and the blood platelet antibody and pose as a problem thepossibility of the antibodies giving rise to secondary reactions. As asolution to this problem, the practice of removing of white blood cellsand blood platelets from the whole-blood preparations and the red bloodcell preparations has been heretofore in vogue. As means for theseparation of blood components, specifically for the removal of whiteblood cells and blood platelets from the whole blood or from the redblood component, there has been proposed an apparatus which is obtainedby filling a housing with defatted and bleached Egyptian cotton inuniform density (Japanese Patent Publication NO. SHO 55(1980)-23,805).

When an apparatus of this nature is used, however, the degree with whichthe removal of white blood cells and blood platelets is attained hingeson he density of packing of the Egyptian cotton and the efficiency ofthis removal is improved but the speed of passage of blood throughaggregate of cotton is lowered and the time required for the treatmentis lengthened in proportion as the density of packing is increased.Conversely, the speed of passage of blood is heightened but theefficiency of removal is lowered in proportion as the density of packingis lowered. Thus, the apparatus is hardly practicable.

An object of this invention, therefore, is to provide a novel apparatusfor the removal of blood components.

Another object of this invention is to provide an apparatus for theseparation of blood components, which permits quick passage of bloodunder treatment and warrants a reduction in the time for the treatmentat no sacrifice of the efficiency of removal of white blood cells andblood platelets.

DISCLOSURE OF THE INVENTION

The objects described above are accomplished by an apparatus for theseparation of blood components, which comprises a tubular housingprovided at one end thereof with a blood inlet and at the other endthereof with a blood outlet and a layer of aggregate of fibers capableof sequestering white blood cells and blood platelets packed in thehousing, the layer of aggregate of fibers comprising of a blood inletside layer having a bulk density of not less than 0.16 g/cm³ and lessthan 0.21 g /cm³ and a blood outlet side layer having a bulk density ofnot less than 0.21 g/cm³ and not more than 0.23 g/cm³ and being packedat a density in the range of 0.04 to 0.09 g per ml of the flow volume ofblood under treatment.

This invention also concerns an apparatus for the separation of bloodcomponents, wherein the fibers packed in the form of a layer ofaggregate are single fibers. This invention further concerns anapparatus for the removal of blood components, wherein the fibers arenatural fibers such as of cotton or synthetic fibers such as ofpolyester, polyacrlylonitrile, polyamide, or cellulose acetate. Thisinvention concerns an apparatus for the separation of blood components,wherein the fibers are defatted and bleached fibers of Egyptian cotton.This invention also concerns an apparatus for the separation of bloodcomponents, wherein the blood inlet side layer comprises a first layerhaving a blood inlet side bulk density of not less than 0.16 g/cm³ andless than 0.19 g/cm³ and a second layer having a blood outlet side bulkdensity of not less than 0.19 g/cm³ and less than 0.21 g/cm³.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a partially sectioned side view of a typical apparatus for theseparation of blood components as one embodiment of the presentinvention,

FIG. 2 is a cross section of a typical apparatus as another embodimentof the invention, and

FIG. 3 is an artist's concept of a typical method for the use of theapparatus for the separation of blood components illustrated in FIG. 1.

BEST MODE FOR CARRYING OUT THE INVENTION

Now, the present invention will be described in detail below withreference to the accompanying drawings

An apparatus 40 for the separation of blood components illustrated asone embodiment of the present invention in FIG. 1 has fiber aggregatelayers 16 and 18 differing mutually in bulk density packed in a tubularhousing 14 which is provided at one end thereof with a blood inlet 10and at the other end thereof with a blood outlet 12. The fiber aggregatelayers 16 and 18 are formed of fibers capable of sequestering whiteblood cells and blood platelets. The layer 16 which falls on the bloodinlet side possesses a bulk density of not less than 0.16 g/cm³ and lessthan 0.21 g/cm³, preferably not less than 0.17 g/cm³ and less than 0.19g/cm³, and the layer 18 which falls on the blood outlet side possesses abulk density of not less than 0.21 g/cm³ and not more than 0.23 g/cm³,preferably not less than 0.21 g/cm³ and not more than 0.22 g/cm³. Theratio by weight of the blood inlet side layer 16 to the blood outletside layer 18 so packed in the housing is in the range of 80:70 to50:50, preferably 75:25 to 60:40.

The housing 14 is provided near the blood inlet 10 and the blood outlet12 each with a filter 20 which is adapted to prevent the fiber aggregatefrom loss due to disintegration or entrainment. To the blood inlet 10 isconnected a tube 28 which is generally provided at the leading ends ofthe branching legs thereof with hollow needless 24a, 24b and optionallyprovided halfway along the lengths of the branching legs thereof withclamps 26a, 26b. To the blood outlet 12 is connected a tube 34 which isprovided at the leading end thereof with a liquid mixing port 30 andoptionally provided halfway along the length thereof with a clamp 32.

FIG. 2 illustrates another embodiment of this invention. In an apparatus140 similar to the apparatus of the embodiment of FIG. 1, a layercorresponding to the blood inlet side layer 16 comprises a first layer116a and a second layer 116b differing mutually in bulk density.Specifically, inside a tubular housing 124 provided at the upper endthereof with a blood inlet 120 and at the lower end thereof with a bloodoutlet 122, there are disposed a first blood inlet side layer 116a of abulk density of not less than 0.16 g/cm³ and less than 0.19 g/cm³,preferably not less than 0.17 g/cm³ and less than 0.18 g/cm³, a secondblood inlet side layer 116b of a bulk density of not less than 0.19g/cm³ and less than 0.21 g/cm³, preferably not less than 0.19 g/cm³ andless than 0.20 g/cm³, and a blood outlet side layer 118 of a bulkdensity of not less than 0.21 g/cm³ and not more than 0.23 g/cm³,preferably not less than 0.21 g/cm³ and not more than 0.22 g/cm³, asincreasingly separated from the blood inlet 120 side of the housing 124.The ratio by weight of the blood inlet side layer (the sum of the firstlayer 116a and the second layer 116b) to the blood outlet side layer 118packed in the housing is in the range of 80:20 to 50:50, preferably75:25 to 60:40, and the ratio by weight of the first layer 116a to thesecond layer 116b is in the range of 70:30 to 30:70, preferably 60:40 to40:60. The reference numerals of FIG. 2 which are the sums of those ofFIG. 1 respectively plus 100 denote the same parts as those of FIG. 1.

If the bulk density of the blood inlet side layer 16 or 116a and 116band the bulk density of the blood outlet side layer 18 or 118 are largerthan the respective upper limits of the aforementioned ranges, the speedof flow of blood is unduly low. If they are smaller than the respectivelower limits, the ratios of removal of white blood cells and bloodplatelets are unduly low. The ratio of packing of the fiber aggregate isin the range of 0.04 to 0.09 g, preferably 0.05 to 0.07 g per ml of theflow volume of blood under treatment. If the ratio of packing is lessthan 0.04 g, the efficiency of removal of white blood cells and bloodplatelets is unduly low. If it exceeds 0.09 g, the resistance to theflow of blood is too large to obtain a satisfactory speed of flow.

To be suitably used for the present invention, the fibers selected areonly required to be capable of sequestering white blood cells and bloodplatelets. As examples of fibers satisfying the requirement, naturalcottons such as Egyptian cotton, American cotton, and Asian cotton andsynthetic fibers such as of polyester, polyacrylonitrile, polyamide, andcellulose acetate can be cited. These fibers are used in the form ofstaple fibers having diameters in the range of 10 to 25 microns,preferably 13 to 18 microns and lengths in the range of 20 to 40 mm,preferably 30 to 40 mm. Among other species of fibers enumerated above,defatted and bleached fibers of Egyptian cotton prove to be particularlydesirable.

Natural cottons are broadly classified under three kinds by districts ofproduction, i.e. Egyptian cotton (Gossypium barbadense), American cottonor Upland cotton (G. hirsutum), and Asian cotton or Indian cotton (G.atrboreum or G. herbaceum). The average fiber length, average diameter,and twists of these cottons are as follows.

    ______________________________________                                                    Average fiber                                                                            Average diameter                                                                           Twist                                     Kind        length (mm)                                                                              (microns)    (/cm)                                     ______________________________________                                        Egyptian cotton                                                                           35.6       16.3          70-112                                   Upland cotton                                                                             25.4       20           56-96                                     Asian cotton                                                                              20         21           48-76                                     ______________________________________                                    

In these cottons, the Egyptian cotton which is a natural cotton havingthe largest average fiber length and the smallest average diameter showsthe highest ratio of removal of white blood cells and blood platelets.Preferably, the natural cotton is used in a defatted and bleached form.The defatting and bleaching of fibers is carried out by following withnecessary modifications the method for production of absorbent cottonspecified in the Japanese pharmacopoeia, i.e. by treating the fiberswith the combination of sodium hydroxide and hypochlorous acid or thecombination of sodium hydroxide and hydrogen peroxide. By thistreatment, the Egyptian cotton or other natural cotton is deprived ofimpurities and is thence prevented from releasing colored substances andimpurities through oxidation.

The housing is not specifically required to have cylindrical shape butallowed to have the shape of a column of a desired section. The materialfor this housing may be polyethylene, polypropylene, vinyl chlorideresin, polystyrene, ABS resin, or polycarbonate. Among other materialscited above, the ABS resin proves to be particularly desirable.

The specific forms of blood which the apparatus of this invention isprincipally intended to separate are fresh blood incorporating therein asuitable anticoagulant and a concentrated solution of red blood cells.This invention, however, is not limited thereto. Any liquid containingfloating blood cells can be subjected to separation by the apparatus ofthis invention. As the anticoagulant to be added to fresh blood, therecan be used heparin, ACD (acid-citrate-dextrose) liquid, or CPD(citrate-phosphate-dextrose) liquid. When the concentrated solution ofred blood cells is to be separated, it has the hematocrit value thereofadjusted in the range of 40 to 60 by the addition of physiologicalsaline solution before it is put to use. The operation of separation ofthe blood by the use of apparatus of this invention is carried out at atemperature in the range of 0° to 38° C. Practical use of the apparatus40 (or 140) of the present invention for the separation of bloodcomponents is effected by connecting the hollow needle 24a to acontainer 42 holding either whole blood or a concentrated solution ofred blood cells (blood bag) and the hollow needle 24b to a container 44holding the physiological saline solution, connecting the blood outlet12 to a hollow needle 46 for further communication via a forked tube 48with blood bags made of vinyl chloride resin or empty containers 50, 52made of glass, closing the clamp 26a, and then opening the clamp 26bthereby allowing the physiological saline solution held in the container44 to flow into the apparatus 40 for separation of blood components,wash the fiber aggregate layers 16, 18, and depart from the blood outletand flow into the empty container 52. Actual use of the apparatus forseparation of the concentrated solution of red blood cells is effectedby opening the clamps 26a, 26b and closing the clamp 54 therebyadvancing the flow of the phsyiological saline solution to the blood bag42 and adjusting the hematocrit value of the red blood cells in therange of 40 to 60, then closing the clamp 26b and opening the clamp 54thereby allowing the blood to flow into the apparatus 40, depart fromthe blood outlet, and enter another empty container 50, and closing theclamp 26a and opening the clamp 26b thereby allowing a suitable amountof the physiological saline solution to flow through and wash the fiberaggregate layers 16, 18, and finally enter the empty container 50. Forthe separation of whole blood, it is not always necessary to use thephysiological saline solution for adjusting the hematocrit value. Theapparatus 140 illustrated in FIG. 2 is used in the same way as theapparatus 40 of FIG. 1.

During the operation described above, when the blood flowing in throughthe blood inlet 10 is passing through the blood inlet side layer 16, ofthe fiber aggregate layers 16, 18, chiefly white blood cells and bloodplatelets which have relatively large particle diameters correspondingto the size of interstices proper to the bulk density of the layer 16are first sequestered. The portions of white blood cells and bloodplatelets which have escaped the sequestration are captured in the bloodoutlet side layer 18. Thus, the fiber aggregate layers 16, 18 sufferfrom far less clogging and permit much quicker flow of blood than afiber aggregate layer which is packed in a uniform bulk density.

The expression "sequestration of white blood cells and blood platelets"as used in the present invention means accumulation of white blood cellsand blood platelets in the aggregates of fibers packed in the apparatus.

Now, the present invention will be described more specifically belowwith reference to working examples. The terms "ratio of removal" and"ratio of recovery" used in the following working examples are definedas follows. ##EQU1##

EXAMPLE 1

An apparatus 40 for the separation of blood components configurated asillustrated in FIG. 1 was fabricated by filling a tubular housing 14made of ABS resin with defatted and bleached Egyptian cotton packed (ina total amount of 26 g) in two layers, i.e. a blood inlet side fiberaggregate layer 16 of a bulk density of 0.18 g/cm³ and a blood outletside fiber aggregate layer 18 of a bulk density of 0.22 g/cm³. A liquidcontaining floating red blood cells (having a hematocrit value of 50)prepared by adding about 100 ml of phsiological saline solution to 250ml of a concentrated solution of red blood cells 5 days old from thetime of collection was caused to flow down into the apparatus at atemperature of 4° to 6° C. via the blood inlet 10 to determine ratio ofremoval of white blood cells, ratio of removal of blood platelets, ratioof recovery of red blood cells, and time for passage of blood. Theresults were as shown in Table 1.

Control 1

The same test was carried out by following the procedure of Example 1,except that the housing 14 was filled with defatted and bleachedEgyptian cotton packed (in a total amount of 22 g) as a fiber aggregatein a uniform bulk density of 0.22 g/cm³. The results were as shown inTable 1.

EXAMPLE 2

The same test was carried out by following the procedure of Example 1,except that whole blood 5 days old from the time of collection was usedin place of the solution containing floating red blood cells. Theresults were as shown in Table 1.

Control 2

The same test was carried out by following the procedure of control 1,except that whole blood 5 days old from the time of collection was usedin place of the solution containing floating red blood cells. Theresults were as shown in Table 1.

EXAMPLE 3

An apparatus 140 for the separation of blood components configurated asillustrated in FIG. 2 was fabricated by filling a tubular housing 114made of ABS resin with defatted and bleached Egyptian cotton packed (ina total amount of 26 g) in three layers, i.e. a first blood inlet sidefiber aggregate layer 116a of a bulk density of 0.18 g/cm³, a secondblood inlet side fiber aggregate layer 116b of a bulk density of 0.20g.cm³, and a blood outlet side fiber aggregate layer 118 of a bulkdensity of 0.22 g/cm³ A liquid containing red blood cells (having ahematocrit value of 50) prepared by adding about 100 ml of physiologicalsaline solution to 250 ml of a concentrated solution of red blood cells5 days old from the time of collection as caused to flow down into theapparatus at a temperature of 4° to 6° C. via the blood inlet 110 fordetermination of the same physical constants as in Example 1. Theresults were as shown in Table 1.

EXAMPLE 4

The same test was performed by following the procedure of Example 3,except that whole blood 5 days old from the day of collection was usedin place of the solution containing floating red blood cells. Theresults were as shown in Table 1.

                  TABLE 1                                                         ______________________________________                                                  Ratio of  Ratio of  Ratio of                                                  removal of                                                                              removal of                                                                              recovery of                                                                           Time for                                          white blood                                                                             platelets red blood                                                                             passage                                 No.       cells (%) (%)       cells (%)                                                                             (min.)                                  ______________________________________                                        Example 1 96        97        96      20                                      Example 2 96        97        96      25                                      Example 3 96        97        96      15                                      Example 4 96        97        96      20                                      Control 1 96        97        94      35                                      Control 2 96        97        94      40                                      ______________________________________                                    

Industrial Applicability

As described in detail above, the apparatus for separation of bloodcomponents according to this invention is configurated so that fiberscapable of sequestering white blood cells and blood platelets are packedin two or three layers having magnitudes of bulk density increasing inthe direction from the blood inlet side to the blood outlet side of thehousing. In the actual separation of blood components, therefore, thisapparatus removes white blood cells and blood platelets in substantiallythe same ratios as an apparatus having the same fibers packed in auniform bulk density and yet manifests a conspicuous effect of notablyshortening the time required for the treatment. It also has an advantagethat the ratio of recovery of red blood cells is improved.

I claim:
 1. An apparatus for separating white blood cells and bloodplatelets from blood, comprising:a tubular housing having at one endthereof a blood inlet and at another end thereof a blood outlet; aplurality of layers of staple fibers of bleached Egyptian cotton capableof sequestering white blood cells and blood platelets packed in saidhousing in the direction of flow of blood through said housing betweensaid blood inlet and outlet; said layers of fibers comprising a bloodinlet side fiber layer adjacent said blood inlet and a blood outlet sidefiber layer adjacent said blood outlet, said blood inlet side fiberlayer having a bulk density of not less than 0.16 g/cm³ and not morethan 0.21 g/cm³, and said blood outlet side fiber layer having a bulkdensity of not less than 0.21 g/cm³ and not more than 0.23 g/cm³ ; saidplurality of layers of fibers being packed in a ratio in the range of0.04 to 0.09 g per ml of the flow volume of blood under treatment bysaid apparatus; and wherein the ratio by weight of said blood inlet sidefiber layer to said blood outlet side fiber layer is in the range of75:25 to 60:40, and wherein the fibers of both said blood inlet sidefiber layer and blood outlet side fiber layer are substantially the sameexcept for their respective bulk densities.
 2. An apparatus according toclaim 1, wherein said blood inlet side fiber layer comprises a firstfiber layer of bulk density of not less than 0.16 g/cm³ and not morethan 0.19 g/cm³ on the blood inlet side thereof, and a second fiberlayer of a bulk density of not less than 0.19 g./cm³ and not more than0.21 g/cm³ on the blood outlet side thereof.
 3. An apparatus accordingto claim 2, wherein the ratio by weight of said first fiber layer tosaid second fiber layer of said blood inlet side fiber layer is in therange of 60:40 to 40:60.